Intracellular sodium elevation reprograms cardiac metabolism

Aksentijevic, Dunja, Karlstaedt, Anja, Basalay, Marina , O'Brien, Brett, Sanchez-Tatay, David, Eminaga, Seda, Thakker, Alpesh, Tennant, Daniel, Fuller, William, Eykyn, Thomas, Taegtmeyer, Heinrich and Shattock, Michael (2020) Intracellular sodium elevation reprograms cardiac metabolism. Nature Communications, 11 (1). ISSN 2041-1723

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Intracellular sodium elevation reprograms cardiac metabolism
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Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodeling occurs. We assessed whether acute (75μM ouabain 100nM blebbistatin) and chronic myocardial Naiload (PLM3SA mouse) are causally linked to metabolic remodeling and whether the hypertrophied failing heart shares a common Na-mediated metabolic ‘fingerprint’. Control (PLMWT), transgenic (PLM3SA), ouabain treated and hypertrophied Langendorff-perfused mouse hearts were studied by 23Na, 31P, 13C NMR followed by 1H NMR metabolomic profiling. Elevated Nai leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorated the metabolic changes. In silico modelling indicated altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Nai overload or inhibition of Na/Camitomay be a new approach to ameliorate metabolic dysregulation in heart failure.

Keywords:Cardiovascular diseases, Energy metabolism, Mechanisms of disease, Metabolomics
Divisions:College of Science > School of Chemistry
ID Code:42126
Deposited On:19 Aug 2020 15:30

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